This year prostate cancer will afflict 189,000 new patients in the United States[l]. In many, the significant burden of tumor will be localized within a portion of the gland. New MRI techniques, including MR Spectroscopy and dynamic MRI, are becoming increasingly able to define the extent of disease in these patients. However, current therapies for prostate cancer are either systemic, or treat the entire gland. We believe advances in MRI guidance will enable minimally invasive, super-selective, targeted cryosurgery as an outpatient treatment for localized disease with minimal risk and morbidity. Potential advantages of MRI guidance over sonography are: Monitoring the entire 3D iceball boundary. Mapping tissue temperature inside the iceball non-invasively. The key to successful cryosurgery is achieving a sufficiently low freezing temperature. Determining the extent and lethality of the cryo-lesion. This would enable re-freezing of any under-treated areas during the same procedure. We will pursue two specific aims to develop MRI guidance technology for prostate cryosurgery: 1 . Calibrate MRI-Thermometry during cryosurgery of prostate cancer: Refine MRI thermometry for human use. [unreadable] Calibrate MRI-thermometry in 25 prostate cancer patients. We will also assess the efficacy, and morbidity of MRI-guided cryoablation 2. Develop advanced MRI to assess acute and chronic cryo-induced injury: Refine perfusion- and diffusion-weighted MRI for imaging immediately after cryosurgery Evaluate post-cryo perfusion- and diffusion-MRI for depicting acute ischemia and cellular injury in animals and tumor necrosis in humans. Evaluate post-cryo perfusion- and diffusion-weighted MRI for predicting ultimate volume of lethal cryoablation in an animal survival model. Completing these aims will pave the way for future clinical trials that definitively measure the efficacy of MRI-guided selective cryoablation compared to other treatments for localized prostate cancer.